Molecule hierarchy

During drug development, active pharmaceutical ingredients are often formulated as salts to provide the final pharmaceutical product. ChEMBL includes parent molecules and their salts (approved and investigational) as well as other alternative forms such as hydrates and radioisotopes. These alternative forms are linked to their parent compound through the molecule hierarchy. 

Using the molecule hierarchy

The molecule hierarchy can be used to retrieve and display connected compounds and to aggregate activity data that has been mapped to any member of a compound family. On the interface, related compounds are automatically displayed in the ‘Alternative forms’ section of the ChEMBL compound report card. Bioactivity data can easily be aggregated in the activity summary by using the 'Include/Exclude Alternative Forms' filter.

Finding the molecule hierarchy

 

On the interface, we include alternative forms as shown above. The downloaded database contains the molecule_hierarchy table and the equivalent API endpoint is the ‘molecule_form’ (https://www.ebi.ac.uk/chembl/api/data/molecule_form).

Example: using the molecule hierarchy to retrieve drug mechanisms

 

One of the most common questions we’re asked is ‘how to obtain drug mechanisms mapped to any member of a compound family’ and so we've provided a couple of examples below.

From the ChEMBL interface

 

The ‘Drugs’ and ‘Mechanism’ views contain only parent molecules and so mechanisms are automatically mapped to the parent form. However, a general search through the ‘Compounds’ view provides mechanisms mapped to parents and all approved salts which can be found on their respective compound report cards.

From the database with SQL

 

In the downloaded database, the drug mechanism may be mapped to a single member of the compound family in the drug_mechanism table, typically the approved form. For example, the mechanism for atorvastatin is mapped to the calcium salt. However, the molecule hierarchy can be used to link the compound family so that a search using the parent (atorvastatin, CHEMBL1487) returns the mechanism mapped to the approved salt (atorvastatin calcium):

 

select *

from drug_mechanism

where molregno in

    (select molregno

    from molecule_hierarchy

    where (

        parent_molregno in

        (select distinct molregno from molecule_dictionary where chembl_id = 'CHEMBL1487') 

        or molregno in

        (select distinct molregno from molecule_dictionary where chembl_id = 'CHEMBL1487')

               )

     );

Questions? 

Please get in touch on the Helpdesk or have a look through our training materials, recent webinar and FAQs.